CN114573457A - Preparation method of malonic half ester - Google Patents
Preparation method of malonic half ester Download PDFInfo
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- CN114573457A CN114573457A CN202210308729.XA CN202210308729A CN114573457A CN 114573457 A CN114573457 A CN 114573457A CN 202210308729 A CN202210308729 A CN 202210308729A CN 114573457 A CN114573457 A CN 114573457A
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- malonate
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- reaction substrate
- ester
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- 238000002360 preparation method Methods 0.000 title claims abstract description 6
- 150000002148 esters Chemical class 0.000 title claims description 8
- 238000006243 chemical reaction Methods 0.000 claims abstract description 40
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 claims abstract description 19
- 239000003054 catalyst Substances 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 12
- OFOBLEOULBTSOW-UHFFFAOYSA-N Malonic acid Chemical compound OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims abstract description 11
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 10
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 24
- XLOMVQKBTHCTTD-UHFFFAOYSA-N Zinc monoxide Chemical compound [Zn]=O XLOMVQKBTHCTTD-UHFFFAOYSA-N 0.000 claims description 18
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 12
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 12
- 239000000758 substrate Substances 0.000 claims description 11
- 239000003513 alkali Substances 0.000 claims description 10
- 239000012074 organic phase Substances 0.000 claims description 10
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- 239000011787 zinc oxide Substances 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 claims description 6
- 239000007795 chemical reaction product Substances 0.000 claims description 6
- 238000001914 filtration Methods 0.000 claims description 6
- 239000003960 organic solvent Substances 0.000 claims description 6
- 238000010992 reflux Methods 0.000 claims description 6
- 239000007787 solid Substances 0.000 claims description 6
- 239000002904 solvent Substances 0.000 claims description 6
- 150000001875 compounds Chemical class 0.000 claims description 5
- 238000001035 drying Methods 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 4
- 238000004821 distillation Methods 0.000 claims description 4
- 239000002585 base Substances 0.000 claims description 3
- 239000002245 particle Substances 0.000 claims description 3
- 230000035484 reaction time Effects 0.000 claims description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 3
- 239000012071 phase Substances 0.000 claims description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 2
- 239000007788 liquid Substances 0.000 claims 1
- -1 malonic acid ester Chemical class 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 2
- 230000007062 hydrolysis Effects 0.000 abstract 1
- 238000007086 side reaction Methods 0.000 abstract 1
- 230000002194 synthesizing effect Effects 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 17
- 238000003786 synthesis reaction Methods 0.000 description 5
- 150000005690 diesters Chemical class 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 230000015572 biosynthetic process Effects 0.000 description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
- 125000004185 ester group Chemical group 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 2
- 239000003814 drug Substances 0.000 description 2
- 229940079593 drug Drugs 0.000 description 2
- 229930014626 natural product Natural products 0.000 description 2
- 238000007142 ring opening reaction Methods 0.000 description 2
- 238000001308 synthesis method Methods 0.000 description 2
- LTMRRSWNXVJMBA-UHFFFAOYSA-L 2,2-diethylpropanedioate Chemical compound CCC(CC)(C([O-])=O)C([O-])=O LTMRRSWNXVJMBA-UHFFFAOYSA-L 0.000 description 1
- PBVZQAXFSQKDKK-UHFFFAOYSA-N 3-Methoxy-3-oxopropanoic acid Chemical compound COC(=O)CC(O)=O PBVZQAXFSQKDKK-UHFFFAOYSA-N 0.000 description 1
- HGINADPHJQTSKN-UHFFFAOYSA-M 3-ethoxy-3-oxopropanoate Chemical compound CCOC(=O)CC([O-])=O HGINADPHJQTSKN-UHFFFAOYSA-M 0.000 description 1
- IYXGSMUGOJNHAZ-UHFFFAOYSA-N Ethyl malonate Chemical compound CCOC(=O)CC(=O)OCC IYXGSMUGOJNHAZ-UHFFFAOYSA-N 0.000 description 1
- 239000012670 alkaline solution Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- BEPAFCGSDWSTEL-UHFFFAOYSA-N dimethyl malonate Chemical compound COC(=O)CC(=O)OC BEPAFCGSDWSTEL-UHFFFAOYSA-N 0.000 description 1
- MOJJCFBDUWMVJK-UHFFFAOYSA-N dipentyl propanedioate Chemical compound CCCCCOC(=O)CC(=O)OCCCCC MOJJCFBDUWMVJK-UHFFFAOYSA-N 0.000 description 1
- LWIWFCDNJNZEKB-UHFFFAOYSA-N dipropyl propanedioate Chemical compound CCCOC(=O)CC(=O)OCCC LWIWFCDNJNZEKB-UHFFFAOYSA-N 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C67/00—Preparation of carboxylic acid esters
- C07C67/30—Preparation of carboxylic acid esters by modifying the acid moiety of the ester, such modification not being an introduction of an ester group
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Catalysts (AREA)
Abstract
The invention discloses a preparation method of half-ester of malonic acid, which can carry out selective hydrolysis on the malonic acid ester in the presence of a catalyst to obtain a half-ester compound. Compared with other methods for synthesizing half-ester of malonic acid, the selective mono-hydrolysis reaction has the advantages of simple reaction conditions, mildness and less side reactions. The catalyst is utilized to promote the mono-hydrolysis reaction of the malonate, so that the reaction activity is high, the yield is high, and the application potential is huge.
Description
Technical Field
The invention relates to a preparation method of malonic half ester, and concretely relates to malonic half ester obtained by carrying out alkaline hydrolysis reaction on malonic ester by using nano zinc oxide as a catalyst.
Background
The half-ester is a compound having both an ester group and a carboxyl group on a molecule, and is one of essential materials in the synthesis process of many important compounds, such as drugs, natural products, polymers and the like, so the synthesis method of the half-ester has been concerned by many researchers. The synthesis method of the half ester includes ring opening of cyclic acid anhydride, mono-hydrolysis reaction of symmetric diester, etc. The ring-opening reaction of the cyclic anhydride is usually carried out in a dry anhydrous organic solvent such as toluene, benzene, ether or chloroform, and the reaction conditions are severe. Relatively speaking, the mono-hydrolysis reaction of the symmetric diester is simple in reaction conditions, can be carried out in an aqueous solution, and is more in line with the times of green chemistry. The mono-hydrolysis reaction of symmetrical diesters is under constant investigation.
The half-ester molecule has two structures of ester group and carboxyl group, and the different reactivity of the ester group and the carboxyl group is an important precursor for constructing a plurality of compounds. Monomethyl malonate and monoethyl malonate, which are important intermediates for the synthesis of many drugs and natural products, are the most commonly used half-esters in organic synthesis, and the diester is efficiently and selectively mono-hydrolyzed, and both half-esters can be obtained in higher yield. This selective mono-hydrolysis reaction is environmentally friendly and simple compared to other methods of synthesis of half esters of malonic acid, since it requires only water, a small fraction of volatile co-solvents and inexpensive reagents, and does not produce harmful by-products, and is therefore of considerable utility in chemical synthesis.
Disclosure of Invention
Aiming at the defects in the prior art, the invention provides a method for preparing malonic acid half ester by using nano zinc oxide as a catalyst for malonate to perform alkaline hydrolysis reaction.
The specific technical scheme of the invention is as follows:
a preparation method of half-ester malonate comprises the following steps:
the method comprises the following specific steps: the malonate reaction substrate is subjected to hydrolysis reaction under the action of a catalyst and dilute alkali to obtain the malonate monoester compound.
Further, R in the malonate reaction substrate is C1-C5, preferably R is C1; the catalyst is nano zinc oxide with the particle size of 10-500 nm, preferably 200 nm; the dilute alkali is one or more of NaOH, LiOH, KOH and Ca (OH)2, and the concentration is 0.1-5.0 mol/L.
Further, the molar ratio of the malonate reaction substrate to the catalyst to the base is 1: 0.5% -2%: 1-10, preferably 1: 1%: 2.
further, the reaction substrate, the catalyst and the alkali are heated in an organic solvent for reflux reaction.
Further, the reaction time is 3-8 h; the organic solvent is one or more of acetone, tetrahydrofuran and toluene, and the dosage of the solvent is 10 times of the mass of the malonate reaction substrate.
Further, after the reaction is finished, filtering and separating out solids, adding dilute hydrochloric acid into the reaction solution to adjust the pH value of the solution to be 3, separating and collecting an organic phase, extracting a water phase by using ethyl acetate, wherein the using amount of the ethyl acetate is the same as that of the solvent. And combining organic phases, drying the organic phases by anhydrous magnesium sulfate, and then carrying out reduced pressure distillation to obtain a reaction product.
The method utilizes the catalyst to promote the mono-hydrolysis reaction of the malonate, has high reaction activity and high yield, and has great application potential.
Detailed Description
The invention is further illustrated by the following specific examples, which are not intended to be limiting and whose scope is indicated in the claims.
Example 1
Adding 10 g of dimethyl malonate, 1% of nano zinc oxide in molar weight, 2 times of alkaline solution in molar weight and 100 g of organic solvent into a reaction bottle, heating and refluxing for reaction, filtering and separating out solids after the reaction is finished, adding dilute hydrochloric acid into the reaction solution to adjust the pH value of the solution to be 3, extracting the reaction solution by using 100 g of ethyl acetate, wherein the using amount of the ethyl acetate is the same as that of the solvent, drying an organic phase by anhydrous magnesium sulfate, then carrying out reduced pressure distillation to obtain a reaction product, and calculating the experimental yield. In order to obtain the optimal collocation method of multiple factors and various levels, orthogonal experiments are carried out on zinc oxide with different particle sizes of 10-500 nm, different alkalies (NaOH, LiOH and KOH), different reaction time and different solvents.
TABLE 1 orthogonal Experimental Table
Example 2
Adding 10 g of diethyl malonate, 0.5% of nano zinc oxide (200 nm) in molar amount, 10% of LiOH (1 mol/l) alkali solution and 100 g of acetone into a reaction bottle, heating, refluxing, reacting, filtering and separating out a solid, adding dilute hydrochloric acid into the reaction solution to adjust the pH value of the solution to be 3, extracting the reaction solution by 100 g of ethyl acetate, drying an organic phase by anhydrous magnesium sulfate, and distilling under reduced pressure to obtain a reaction product, wherein the yield is 89%.
Example 3
Adding 10 g of dipropyl malonate, 2% of nano zinc oxide (200 nm) in molar amount, 5% of LiOH (1 mol/l) alkali solution and 100 g of acetone into a reaction bottle, heating, refluxing, reacting, filtering and separating out solids after the reaction is finished, adding dilute hydrochloric acid into the reaction solution to adjust the pH value of the solution to be 3, extracting the reaction solution by 100 g of ethyl acetate, drying an organic phase by anhydrous magnesium sulfate, and then distilling under reduced pressure to obtain a reaction product, wherein the yield is 85%.
Example 4
10 g of diamyl malonate, 2 mol percent of nano zinc oxide (200 nm), 2 mol percent of LiOH (1 mol/l) alkali solution and 100 g of acetone are added into a reaction bottle for heating reflux reaction, after the reaction is finished, solids are separated by filtration, dilute hydrochloric acid is added into the reaction solution to adjust the pH value of the solution to be 3, the reaction solution is extracted by 100 g of ethyl acetate, and the organic phase is dried by anhydrous magnesium sulfate and then is subjected to reduced pressure distillation to obtain a reaction product, wherein the yield is 81%.
Claims (6)
1. The preparation method of the malonic acid half ester is characterized by comprising the following steps:
carrying out hydrolysis reaction on a malonate reaction substrate under the action of a catalyst and dilute alkali to obtain a malonate monoester compound; the reaction equation is as follows:
r in the malonate reaction substrate is C1-C5, preferably R is C1; the catalyst is nano zinc oxide with the particle size of 10-500 nm, preferably 200 nm; the dilute alkali is NaOH, LiOH, KOH, Ca (OH)2The concentration of one or more of (A) is 0.1-5.0 mol/L.
2. The method for preparing half malonate according to claim 1, characterized in that: the molar ratio of the malonate reaction substrate to the catalyst to the base is 1: 0.5% -2%: 1-10.
3. The method for preparing half malonate according to claim 1, characterized in that: the molar ratio of the malonate reaction substrate to the catalyst to the base is 1: 1%: 2.
4. the method for preparing half malonate according to claim 1, characterized in that: heating and refluxing a reaction substrate, a catalyst and alkali in an organic solvent for reaction.
5. The method for preparing half malonate according to claim 4, characterized in that: the reaction time is 3-8 h; the organic solvent is one or more of acetone, tetrahydrofuran and toluene, and the dosage of the solvent is 10 times of the mass of the malonate reaction substrate.
6. The method for preparing half malonate according to claim 1, characterized in that: and after the reaction is finished, filtering and separating out a solid, adding dilute hydrochloric acid into the reaction solution to adjust the pH value of the solution to be 3, separating liquid and collecting an organic phase, extracting a water phase by using ethyl acetate, combining the organic phase, drying the organic phase by using anhydrous magnesium sulfate, and then carrying out reduced pressure distillation to obtain a reaction product.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210308729.XA CN114573457B (en) | 2022-03-28 | 2022-03-28 | Preparation method of malonic acid half ester |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202210308729.XA CN114573457B (en) | 2022-03-28 | 2022-03-28 | Preparation method of malonic acid half ester |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN114573457A true CN114573457A (en) | 2022-06-03 |
| CN114573457B CN114573457B (en) | 2024-06-14 |
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| CN202210308729.XA Active CN114573457B (en) | 2022-03-28 | 2022-03-28 | Preparation method of malonic acid half ester |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110283103A (en) * | 2019-06-27 | 2019-09-27 | 北京理工大学 | A kind of decarboxylation amination of base catalysis prepares amino-acid ester/amide method |
| WO2021170464A1 (en) * | 2020-02-28 | 2021-09-02 | Basf Se | Herbicidal malonamides |
-
2022
- 2022-03-28 CN CN202210308729.XA patent/CN114573457B/en active Active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110283103A (en) * | 2019-06-27 | 2019-09-27 | 北京理工大学 | A kind of decarboxylation amination of base catalysis prepares amino-acid ester/amide method |
| WO2021170464A1 (en) * | 2020-02-28 | 2021-09-02 | Basf Se | Herbicidal malonamides |
Non-Patent Citations (1)
| Title |
|---|
| SHANG RUI 等: "Synthesis of a-Aryl Nitriles through Palladium-Catalyzed Decarboxylative Coupling of Cyanoacetate Salts with Aryl Halides and Triflates", ANGEW. CHEM. INT. ED., 6 April 2011 (2011-04-06), pages 4470 - 4474 * |
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| Publication number | Publication date |
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| CN114573457B (en) | 2024-06-14 |
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